Study Rationale:
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by loss of neurons in the substantia nigra, a brain region that controls motion. This loss leads to motor dysfunctions such as tremor, slow movement, rigid muscles and impaired balance. Although the majority of cases of PD appear to be sporadic, mutations in multiple genes — including the gene LRRK2 — have been found in families with a history of disease. We propose to examine whether a combination of genetic and environmental factors might influence the age at onset and disease progression in PD that is either idiopathic or associated with LRRK2.
Hypothesis:
Our overall hypothesis is that environmental and lifestyle factors can influence the age at onset and both motor and non-motor features in idiopathic or sporadic PD and in LRRK2-associated PD.
Study Design:
We will use the Fox Insight Data Exploration Network questionnaires on smoking and tobacco use, caffeine consumption, anti-inflammatory medication history and pesticide exposure in work and non-work settings to assess whether any of these factors are associated with the age at onset and progression of PD. We will examine dosage effects (such as the number of cigarettes smoked per day or the years of coffee drinking) and the longitudinal effects of aging on motor and non-motor features with the responses participants give over time.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
If we can identify specific environmental factors that lead to a later age at onset and an improvement of PD-related motor and non-motor symptoms, this information will be used to develop a therapeutic strategy to improve the life of people with PD.
Next Steps for Development:
The specific factors identified in this research project can be further explored and broken down into components that will be functionally validated. For example, a protective effect of smoking on disease outcome could be validated on a cellular level by treatment with nicotine.